Among strategies to prevent cancer, clinical nutrition studies play a vital role in the transition from observational research to clinical trials. These studies 1) assess the metabolic effects of dietary changes in humans and 2) determine the safety, toxicity, pharmacokinetics, bioavailability, and mechanisms of action of macro- and micronutrients with chemoprevention potential, thereby providing information necessary to properly plan and conduct intervention studies using such agents or approaches. To further define these parameters in humans, a cooperative research effort between the Beltsville Human Nutrition Research Center in the U.S. Department of Agriculture and the CPSB, DCPC, was initiated in 1983. Since then, clinical nutrition research has been conducted in several areas but most prominently in relation to antioxidants and hormones. Antioxidant research has focused on dose, bioavailability, and safety of selenium, carotenoids, and vitamin C. Hormone research has focused on the potential modulating roles of dietary fat and alcohol. Altogether, over ten different projects have been conducted during this time. Future research will focus on important and promising areas of nutrition and cancer research, including antioxidants; fat, fiber, and energy; phytochemicals; and alcohol.